Search Results (209)

Malaria remains a leading cause of morbidity and mortality among children in sub-Saharan Africa. Acute kidney injury (AKI) is increasingly recognized as a frequent and severe complication of pediatric severe malaria, yet it remains largely underdiagnosed. This under-recognition is driven by important limitations in current diagnostic approaches. The World Health Organization (WHO) criteria rely on fixed serum creatinine (SCr) thresholds that are poorly adapted to children, whereas Kidney Disease Improving Global Outcomes (KDIGO) criteria require baseline SCr (bSCr) values that are rarely available in low-resource settings. The estimation of bSCr using back-calculation methods is further complicated by population-specific factors, particularly malnutrition, which reduces creatinine generation and may mask kidney injury. In addition, urine output (UO) monitoring is often underutilized despite its diagnostic value, and access to laboratory testing remains limited. Emerging biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and kidney injury molecule-1 (KIM-1) show promise for early detection and risk stratification but remain insufficiently validated in African pediatric populations. In this narrative review, we highlight key challenges in diagnosing malaria-associated AKI (MAKI) in children and discuss potential strategies to improve early detection in resource-limited settings, with the aim of reducing morbidity and mortality. Full article

Background/Objectives: Active surveillance (AS) is recommended for men with low-risk prostate cancer to minimize overtreatment while monitoring for disease progression. However, current surveillance strategies rely heavily on repeat biopsies, which are invasive and associated with morbidity. MyProstateScore 2.0—Active Surveillance (MPS2-AS) is a urine-based biomarker test developed to predict progression to Grade Group ≥ 2 (GG ≥ 2) and Grade Group ≥ 3 (GG ≥ 3) prostate cancers in men on AS. The objective of this study was to analytically validate the reproducibility and robustness of MPS2-AS analyte detection and risk score calculation across key laboratory variables. Methods: Analytical precision was evaluated using pooled urine specimens processed using the MPS2-AS laboratory workflow. Eight pooled urine samples were tested in a within-laboratory design across five days, with two runs per day, and two replicates per run. Additional reproducibility studies assessed variability across three QuantStudio™ 12K Flex Real-Time PCR Systems and three OpenArray™ chip lots. Ten RNA biomarkers were quantified by RT-PCR and used to calculate the MPS2-AS GG1-2 and GG1-3 risk scores. Variance components were estimated using hierarchical ANOVA. Results: The MPS2-AS analyte measurements demonstrated high precision across within-laboratory testing, with standard deviations ranging from 0.00 to 0.60 and coefficients of variation (%CV) from 0.00 to 4.01%. The reproducibility across qPCR instruments and OpenArray chip lots showed similar robustness, with analyte %CVs of ≤4.57% and ≤4.10%, respectively. These stable analyte measurements translated to reproducible model outputs, with %CV ≤ 10.69% for the GG1-2 risk score and ≤7.20% for the GG1-3 risk score across all tested conditions. No systematic bias was observed between runs, days, instruments, or reagent lots. Conclusions: MPS2-AS demonstrates strong analytical precision and reproducibility for quantifying urinary biomarkers and generating GG1-2 and GG1-3 risk scores. These results support the reliability of MPS2-AS for clinical laboratory implementation and its use as a non-invasive tool to inform biopsy decisions in men with Grade Group 1 prostate cancer undergoing active surveillance. Full article

Sepsis-associated acute kidney injury (SA-AKI) remains a major diagnostic challenge in critically ill patients, as conventional functional criteria—serum creatinine and urine output—often detect AKI after clinically relevant pathophysiological derangement has already evolved. Increasing evidence suggests that SA-AKI reflects a heterogeneous process characterized by early cellular stress, microcirculatory dysfunction, inflammation-associated injury, and maladaptive repair preceding overt functional decline. In this context, biomarker-based approaches have been investigated to improve early risk stratification, phenotypic characterization, and prognostic assessment in septic patients. This narrative review synthesizes current evidence on established and emerging biomarkers relevant to SA-AKI, encompassing stress markers ([TIMP-2]•[IGFBP7]), tubular injury markers (e.g., NGAL, KIM-1, IL-18), functional markers (e.g., proenkephalin/penKid, cystatin C), and exploratory molecular signatures such as circulating microRNAs (miRNAs). We examine their temporal dynamics, performance estimates, and context-dependent applicability in sepsis, and discuss limitations related to heterogeneity, assay variability, and threshold standardization. Particular attention is given to multimodal and longitudinal strategies integrating biomarkers with KDIGO criteria and clinical phenotyping. Finally, we outline a stratified framework for biomarker interpretation in SA-AKI anchored to pathophysiological windows and clinical decision points. While available evidence supports the potential of selected biomarkers for short-term risk stratification and trajectory assessment, implementation requires prospective validation demonstrating incremental value beyond established models and measurable impact on patient-centered outcomes. Full article

Background: Evaporative water loss from burn wounds is a major but often neglected component of early fluid requirements. Despite its physiological importance, no dedicated review has quantified acute post-burn evaporative water loss (TEWL) and its interaction with modern resuscitation strategies in over 40 years. Recent mass-casualty burn events in specialized centers have re-emphasized the clinical importance of accurate early fluid balance, which is particularly challenging. Methods: A scoping review (PRISMA-ScR) of historical quantitative studies and 23 contemporary (2015–2025) adult major-burn resuscitation cohorts was conducted. Expected TEWL was derived from Lamke benchmarks; interstitial edema was estimated from the only available regression of simultaneous fluid input and 24 h weight change. A novel TEWL/edema ratio was tested against resuscitation volume (mL/kg/%TBSA) and the established input/output (I/O) ratio. Results: In the acute phase, the median TEWL normalized to total body surface area was 71 mL/m²/h [52–79 mL/m²/h], allowing for calculation of the TEWL/edema ratio. The TEWL/edema ratio was inversely correlated with the resuscitation fluid dose (R² = 0.811) and the I/O ratio as well (R² = 0.86), crossing unity at 2.85 mL/kg/%TBSA. A ratio > 1 signals high evaporative drive and/or possible under-resuscitation; a ratio < 1 alerts to fluid creep before significant weight gain. Conclusions: The TEWL/edema ratio is the first physiology-grounded, easily calculable resuscitation endpoint that complements urine output by providing insight into whether administered fluid is lost as obligatory evaporation or sequestered as edema. Routine estimation of expected TEWL and early monitoring of the TEWL/edema ratio may help guide goal-directed burn resuscitation, especially when early excision is delayed or impossible. Given the substantial inter-individual variability, the ratio derived from aggregate data should not be interpreted as a patient-specific predictor. Full article

Background/Objectives: Wolfram syndrome type 1 (WS1) is a rare, progressive, multisystem neurodegenerative disorder characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. As survival has improved, an increasing number of affected women are reaching reproductive age. However, evidence on pregnancy and peripartum management in WS1 remains scarce, and practical guidance is limited. This case report describes the multidisciplinary management of pregnancy and delivery in a woman with genetically confirmed WS1 and highlights key considerations for peripartum care. Case Presentation: A woman with genetically confirmed WS1 and long-standing multisystem involvement, including diabetes mellitus, diabetes insipidus, neurogenic bladder requiring frequent self-catheterization, progressive neurologic manifestations, and severe sensory impairment, achieved pregnancy through assisted reproduction with oocyte donation and was closely monitored by a multidisciplinary team. Due to persistent breech presentation, a planned external cephalic version was performed at 37 + 5 weeks’ gestation with immediate availability for cesarean delivery. After unsuccessful attempts, cesarean delivery was performed under combined spinal–epidural anesthesia. Peripartum management focused on strict glycemic control, careful monitoring of fluid balance and urine output, neuraxial anesthesia with proactive hemodynamic management, precautions related to the cochlear implant, and tailored communication strategies. Postpartum recovery was favorable, although anemia on postoperative day 1 required transfusion of one unit of packed red blood cells and intravenous iron therapy. Discussion and Conclusions: Pregnancy in WS1 represents a high-risk clinical scenario because of the coexistence of endocrine, urologic, and neurologic comorbidities, while published evidence on peripartum management remains limited. This case supports an individualized, multidisciplinary approach to obstetric and anesthetic planning and the use of a practical framework to optimize peripartum management and enhance maternal–fetal safety in this rare condition. Full article

Apolipoprotein epsilon (APOE) is a small molecular protein that regulates lipid and lipoprotein homeostasis. Several reports demonstrated that apolipoprotein epsilon-4 allele (APOE4) expression significantly increases the genetic risk of Alzheimer’s disease (AD) and chronic kidney disease. However, there is inconsistent evidence of the association of AD with dietary habits, especially salt intake. Therefore, we hypothesized that high dietary salt intake would exacerbate cognitive decline in mice expressing the human APOE4 allele. We used human APOE (APOE4 and APOE3) knock-in mice to test this hypothesis. Young adult male and female mice aged 5–7 months old (n = 18 in each group) were fed a 4% NaCl (high-salt) or a 0.1% NaCl (low-salt) diet for 4 weeks. Metabolic cage studies were used to assess 24 h measurements of food and water intake, and urine output. Spatial memory and learning were determined using the Barnes maze test. Both the APOE3 and APOE4 mice on a low-salt diet had significantly decreased urinary volume, and female mice had lower body weight. The APOE4 mice on the low-salt diet (0.1%) performed significantly better on the 72 h probe test as compared to the APOE4 mice on 4% salt diet. The results demonstrate an association among dietary salt, memory, and APOE4 genotype. Full article

Global population growth has intensified the demand for productive and sustainable livestock systems. Lithothamnium calcareum, a calcareous marine alga, has been investigated as a natural feed additive for cattle diets. This study evaluated the effects of L. calcareum supplementation on performance, carcass traits, nutrient digestibility, nitrogen metabolism, urinary and fecal pH, and enteric methane emissions in Nellore heifers during the finishing phase. Thirty-six heifers (BW = 268.8 ± 7.3 kg) were assigned to individual pens in a completely randomized design and fed ad libitum diets (25:75 forage-to-concentrate ratio, DM basis). Treatments were: (1) sodium bicarbonate (110 g/heifer/day) and (2) L. calcareum (60 g/heifer/day). The 96-day trial included 12 days of adaptation and 84 days on the finishing diet. Methane emissions were measured using the sulfur hexafluoride (SF₆) tracer technique. L. calcareum did not affect performance, carcass traits, nitrogen metabolism, or apparent total tract digestibility (all p ≥ 0.106), but reduced urine pH (p ≤ 0.001) and tended to lower methane emissions (−8.2%; p = 0.079). Thus, L. calcareum appears to be a viable natural alternative to sodium bicarbonate in finishing diets for Nellore heifers, maintaining productive performance and potentially reducing enteric methane output. Full article

Barbatic acid (BA), a phenolic compound isolated from Pyrrosia petiolosa (Christ) Ching, was investigated for its diuretic effects and underlying mechanisms following oral administration in rats using UPLC-MS/MS-based metabolomics and pharmacokinetics. In a water-loaded rat model, BA (28 and 56 mg/kg) significantly increased 6 h urine output (1.5-fold vs. model, p < 0.01) and promoted urinary excretion of Na⁺, K⁺, and Cl⁻ (1.1–1.4-fold, p < 0.05–0.01). Metabolomic analysis revealed that BA modulates amino acid metabolism pathways, including cysteine and methionine metabolism (impact score 0.16), tyrosine metabolism (impact score 0.10), histidine metabolism (impact score 0.12), taurine hypotaurine metabolismand (impact score 0.43), and phenylalanine metabolism (impact score 0.14). Pharmacokinetic evaluation showed dose-dependent half-lives of 5.88, 5.23, and 2.61 h at 28, 56, and 112 mg/kg, respectively, with Cmax and AUC increasing proportionally with dose (r² > 0.99). These findings provide the first integrated evidence supporting BA as a potential novel diuretic agent with a mechanism involving amino acid metabolism regulation. Full article

The rapid detection of zinc in different aqueous matrices is very relevant. For example, a Zn²⁺ level above ca. 50 µM affects drinking water quality, while levels below ca. 25 µM in urine are related to higher probability of prostate cancer. Herein, a simple and rapid qualitative colorimetric sensor for the detection of zinc ions in aqueous samples is developed. The sensor exploits the reaction between 1,5-diphenylthiocarbazone and Zn²⁺ to form colored chelates whose color changes with increasing Zn²⁺ concentration. The chelating agent has been immobilized in a dried form on various cellulose- and synthetic-based materials to obtain a sensor that can be used for in situ analysis. The procedure to obtain the colorimetric device is easy and straightforward. Moreover, it requires neither specialized personnel to perform the analysis nor specialized personnel for the interpretation of the analytical results. The analysis requires only 20 µL of sample, and a reliable colorimetric output is obtained within 10 min and is stable up to 30 min. The sensor allows Zn²⁺ visual detection in drinking water and urine without any sample pre-treatment with excellent efficiency and repeatability. Considering the ability to distinguish between Zn²⁺ concentrations equal to 0.5 and 2× the cut-off level, the sensor showed sensitivity and specificity of 100% for fortified tap water analysis and 100% sensitivity and 88.9% specificity for urine samples. The almost-perfect concordance with the reference atomic absorption spectrometer and the 94.1% accuracy demonstrated the sensor’s excellent potential to be applied for selective qualitative Zn²⁺ detection in real-life situations. Full article

Background: Intraoperative high-volume diuresis is a common but under-recognized phenomenon during off-pump coronary artery bypass grafting (OPCABG). Its clinical correlates and implications for perioperative management remain incompletely characterized. Methods: This single-center retrospective cohort study included 1274 adults undergoing elective OPCABG between January and August 2025. High-volume diuresis was defined as urine output ≥ 5 mL·kg⁻¹·h⁻¹. Multivariable logistic regression was used to identify factors independently associated with intraoperative high-volume diuresis. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Results: High-volume diuresis occurred in 39.6% of patients. Older age, hypertension and greater intraoperative fluid infusion were independently associated with high-volume diuresis, whereas preoperative diuretic and greater cumulative exposure to systolic blood pressure < 100 mmHg were inversely associated with diuresis. The multivariable model demonstrated acceptable discrimination (AUC = 0.756). Postoperative outcomes, including acute kidney injury, duration of mechanical ventilation, intensive care unit stay, and hospital length of stay, did not differ between groups. Conclusions: Intraoperative high-volume diuresis during OPCABG reflects complex physiological and hemodynamic responses and can be anticipated based on preoperative and intraoperative factors. These findings support a more individualized interpretation of urine output and perioperative management strategies in OPCABG. Full article

Background/Objectives: This study aimed to evaluate the effects of short-term broccoli powder supplementation on metabolically demanding exercise performance, muscle power, and blood lactate recovery. It also investigated broccoli powder-derived sulforaphane bioavailability and its effects in attenuating exercise-induced oxidative stress. Methods: Seventeen healthy males (age 23.8 ± 4.9 years, height 182.3 ± 6.1 cm, weight 80.0 ± 12.8 kg), in a double-blind crossover design, three weeks apart, consumed ten standard doses of either broccoli powder or spinach powder as a placebo over a period of 2 weeks. They then performed a maximal progressive cycling task with concomitant analysis of expired gas composition. Plasma malondialdehyde (MDA) level was measured before and 60 min after the completion of the task, and blood lactate and muscle power (counter-movement vertical jump (CMJ) performance) were measured before and up to 60 min after exercise. Results: The main findings were that despite urine sulforaphane output being markedly higher following broccoli supplementation (p < 0.05), which confirms effective absorption and systemic availability of the compound, this did not influence exercise-induced changes in plasma MDA concentration, blood lactate dynamics, exercise test performance, or functional recovery measured as muscle power via CMJ performance (p > 0.05). Conclusions: In conclusion, broccoli powder supplementation, despite efficient delivery of sulforaphane, does not seem to either acutely affect performance or modify oxidative stress and recovery from metabolically demanding exercise. Full article

Polyomaviruses establish long-term infection in the kidney and are intermittently shed in urine. However, the relationship between kidney-resident viral genomes and urinary shedding during persistent infection remains poorly defined. Using a genetically barcoded murine polyomavirus library, we tracked thousands of viral lineages in vivo by pairing longitudinal urine sampling with endpoint barcode sequencing of kidney tissue in four mice. Across all animals, kidney infection consistently resolved into two stable viral populations, with near-silent persistence as the dominant fate. Most kidney-resident barcodes were never detected in late urine at late stages of infection, even though many reached substantial abundance within the kidney, demonstrating that kidney viral genome levels alone do not predict urinary shedding. In contrast, only a small minority of kidney barcodes contributed disproportionately to urine virus output at late timepoints, and these barcodes exhibited stable longitudinal behavior, with repeated detection in urine over time and markedly higher peak urine abundance than late non-shed or random barcode controls. Shedding behavior was not explained by input virus stock abundance, barcode sequence features, predicted miRNA targeting, or ongoing reseeding from blood or other tissues. Instead, barcodes that ultimately dominated late urine already showed elevated urine detection early after infection, indicating that shedding fate is established early and maintained throughout persistent infection. Together, these findings reveal that persistent kidney infection is a structured reservoir composed of a large population of deeply restricted viral genomes and a smaller, stable subset that repeatedly produces urine-detectable viruses, with concurrent smoldering infections and latency-like restriction representing one possible model to explain the sharply different probabilities of shedding among kidney-resident genomes. Full article

Background: Obesity has reached epidemic proportions and represents a challenge in selecting the optimal renal replacement therapy for patients with end-stage renal disease (ESRD). This study aimed to evaluate the outcomes of peritoneal dialysis (PD) patients according to baseline body mass index (BMI) and to assess the impact of BMI changes during follow-up on PD-related complications and patient outcomes. Methods: This retrospective, single-center study included 53 incident PD patients treated between June 2006 and August 2015. Based on baseline BMI, patients were classified as normal weight (18.5–24.9 kg/m²; n = 17), overweight (25.0–29.9 kg/m²; n = 25), or obese (≥30.0 kg/m²; n = 11). PD adequacy, mechanical and infectious complications, technique survival, and patient survival were assessed over a 48-month follow-up. The effect of BMI changes during follow-up was also analyzed. Results: At PD initiation, total weekly Kt/V was significantly lower in the obese compared with the normal-weight patients (2.0 ± 0.4 vs. 2.3 ± 0.5; p = 0.038), although values remained within the ISPD targets. The normal-weight patients had lower urine output compared with the overweight patients (p = 0.038). Exit-site infections were the most frequent, whereas peritonitis incidence was the lowest in the obese patients, without statistically significant differences. The obese patients demonstrated poorer technique survival and overall survival, again without statistical significance. Mean BMI change after one year was 1.65 ± 2.08 kg/m², and after 4 years, it was 2.07 ± 3.18 kg/m². The BMI change was not associated with complications or survival. Conclusions: No significant association during the 48-month follow-up period was observed between baseline nutritional status or weight gain assessed by body mass index and adverse peritoneal dialysis outcomes; therefore, overweight and obese patients can achieve adequate PD performance and may defer or avoid transition to hemodialysis. Full article

Background/Objectives: Lower urinary tract symptoms (LUTSs), particularly nocturia and urgency, often intensify during the menopause transition and may worsen with caffeine intake and cold exposure. This review aims to synthesize evidence relevant to a hypothesized caffeine–cold interaction in transitional menopause, focusing on water homeostasis and the estrogen–transient receptor potential melastatin 8 (TRPM8) cold-sensory axis, and to propose potentially actionable, nutrition-centered intervention candidates for future testing. Methods: Structured narrative review of PubMed, Embase, Web of Science, and citation tracking (inception–January 2026). Evidence was mapped into a mechanistic framework distinguishing established from hypothesis-generating links; no formal systematic-review study selection or meta-analysis was performed. Results: Caffeine can increase urine output via renal mechanisms (adenosine receptor antagonism and natriuresis) and may lower bladder sensory thresholds. Because half-life is long and variable, afternoon intake can extend into sleep, potentially increasing awakenings and nocturnal voids. Human studies link colder indoor environments to nocturia/overactive bladder, and passive pre-bedtime heating is associated with fewer nocturnal voids. We propose that repeated nighttime cold may amplify caffeine-related diuresis and may shift urine production toward the night, while estradiol decline may heighten TRPM8-mediated cold sensory gain, potentially contributing to urgency/frequency flares. A testable 2 × 2 cold × caffeine framework can operationalize dose, timing, and metabolism, pairing voiding diaries and bedroom temperature sensing with copeptin profiling. Conclusions: Transitional menopause may represent a susceptibility window in which endocrine instability and estradiol decline could plausibly increase sensitivity to indoor cold exposure and caffeine intake, potentially contributing to nocturia and urgency. The hypothesis label ‘dual hormone suppression’ (attenuated nocturnal AVP signal plus estradiol decline) may provide a mechanistic substrate for cold-exacerbated nocturnal polyuria, while an estrogen–TRPM8 axis may amplify cold-evoked urgency. Potentially actionable candidates include chronobiological caffeine timing/management and low-burden thermal strategies; nevertheless, menopause-stage-specific epidemiologic and clinical evidence for a caffeine × cold interaction remains limited and several mechanistic links are extrapolated, so prospective diary- and biomarker-enabled studies and controlled trials are needed to validate mechanisms and refine cold-sensitive endotypes. Full article

Background: Intradialytic hypotension (IDH) in hospitalized patients with acute kidney injury (AKI) is associated with increased morbidity and mortality. Early identification of high-risk patients may enable preventive strategies. This study aimed to identify risk factors for IDH and develop a prediction model in this setting. Method: We conducted a retrospective cohort study of hospitalized patients with dialysis-requiring AKI who underwent conventional renal replacement therapy (RRT). Univariable and multivariable analyses were performed using generalized estimating equations (GEE) to account for repeated dialysis sessions within patients. IDH was defined as systolic blood pressure < 90 mmHg during dialysis. Although external validation was not performed, internal validation of the predictive model was conducted using 10-fold cross-validation. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUROC). Result: A total of 423 hemodialysis sessions from 85 patients were analyzed; the median age was 61 years, and the incidence of IDH session was 35.9%. Multivariable GEE analysis identified residual urine output <100 mL/day (OR 1.78, p = 0.007), vasopressor use (OR 3.36, p < 0.001), prior IDH (OR 2.25, p = 0.002), and lower pre-dialysis mean arterial pressure (MAP 80–89 mmHg: OR 2.43, p = 0.002; MAP < 80 mmHg: OR 2.95, p < 0.001) as significant predictors. Serum albumin < 2.5 g/dL was retained in the final model due to its clinical relevance and contribution to model performance despite borderline significance (OR 1.44, p = 0.08). A weighted integer-based risk score was derived directly from the coefficients of the final multivariable GEE model, stratifying patients into low-, intermediate-, and high-risk groups with IDH incidences of 11.6%, 33.9%, and 56.7%. The model demonstrated good discrimination, with an AUROC of 0.760 (95% CI, 0.714–0.807). Conclusions: The predictive score for IDH demonstrated good performance and highlights the importance of raising awareness to guide interventions aimed at improving the outcomes of hospitalized AKI patients requiring conventional RRT. Full article